Research & Funding


Research Projects

 

"Discovery consists of seeing what everybody has seen, and thinking what nobody has thought"

-Albert Szent-Gyorgi (Nobel Laureate, Physiology or Medicine, 1937)

Our laboratory uses mouse spermatogenesis as a model system to investigate mechanisms that regulate cellular differentiation. Spermatogenesis begins in the neonatal mouse testis with the segregation of precursor prospermatogonia into distinct undifferentiated and differentiating populations of spermatogonia. A proportion of undifferentiated spermatogonia retain stem cell potential (as foundational spermatogonial stem cells, or SSCs), and the remainder becomes progenitor spermatogonia that proliferate and differentiate in response to retinoic acid (RA). This initial fate decision is critical, as imbalances cause spermatogenic defects that can lead to human testicular cancer or infertility. It is currently unknown how mammalian spermatogonial fate decisions are regulated; however, they are critical for maintaining tissue homeostasis, as imbalances cause spermatogenesis defects that can lead to human testicular cancer or infertility. A great deal of effort has been exerted to understand how the SSC population is maintained. In contrast, little is known about the essential program of differentiation initiated by RA that precedes meiosis, and the pathways and proteins involved are poorly defined. A primary reason for this gap in knowledge is there are few reported changes in steady state mRNA levels during differentiation, preventing identification of the full complement of involved gene products to inform focused studies.

To better understand neonatal germ cell differentiation at the onset of spermatogenesis, we are currently: 1 – using transgenic and knockout mice to define the requisite molecular signaling pathways downstream of RA, 2 – determining the role of RA in translational regulation during spermatogonial differentiation, and 3 – defining how RA responsiveness regulates spermatogonial fate and the formation of the foundational SSC pool at the beginning of spermatogenesis.

Funding

We are fortunate to currently have 2 grants from the NIH/NICHD, an R15 funded through 2018 (HD072552), and an R01 funded through 2022 (HD090083).